Studies on regenerative medicine for severe diabetes mellitus by stem cell biology

干细胞生物学对重症糖尿病再生医学的研究

基本信息

批准号：
16390360
负责人：
SUMI Shoichiro
金额：
$ 7.74万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

A new method of making bio-artificial pancreas (BAP), macro-encapsulation of islets in PET (polyethyren tetraphutarate) mesh-reinforced PVA (polyvinyl alcohol) gel by freezing and thawing, was developed. This BAP was found to keep islets viable and functional in comparison to normal free islets in vitro. Transplantation of this BAP ameliorated hyperglycemia and improved renal dysfunction and survival in mouse model of insulin-dependent diabetes mellitus. In studying subcutaneous transplantation of BAP, collagen-coated PVA bag, when applied with sustained release micro-sphere of basic FGF (fibroblast growth factor), was found to induce more angiogenesis and improved viability of included islets in comparison to non-coated PVA bag. Islet preservation studies revealed that apoptosis, a major mechanism of islet cell loss in islet transplantation tended to develop early after islet isolation and rapidly progressed during normal culture conditions. On the other hand, cold preservation in University Wisconsin solution was found to inhibit apoptosis. Pancreas regeneration studies in rats suggested that certain factors perhaps including hyperglycemia was activated by major pancreatectomy and maintained regenerative state of the remnant pancreas, since the weight of the remnant-equivalent pancreas was increased only temporally and returned to its normal weight if pancreatic duct corresponding to removed lobes in major pancreatectomy was ligated and left in the place.In stem cell studies, neuron-like cells obtained in the differentiation studies of mouse embryonic stem cells were found to improve the symptoms of Parkinson's disease in model rats. Differentiation form bone marrow-derived cells and epithelial cells of pancreatic duct to islet cells and electrical cell fusion of bone marrow cells and islet cells were also studied and interesting knowledge toward future studies was accumulated.

开发了一种制造生物人工胰腺（BAP）的新方法，即通过冷冻和解冻将胰岛宏观封装在 PET（聚四丁二酸乙二醇酯）网状增强 PVA（聚乙烯醇）凝胶中。研究发现，与体外正常的游离胰岛相比，这种 BAP 可以保持胰岛的活力和功能。这种 BAP 的移植改善了胰岛素依赖型糖尿病小鼠模型的高血糖症并改善了肾功能障碍和生存率。在研究 BAP 皮下移植时，发现与未涂层 PVA 袋相比，当与碱性 FGF（成纤维细胞生长因子）缓释微球一起使用时，胶原蛋白涂层 PVA 袋可诱导更多血管生成并改善所含胰岛的活力。胰岛保存研究表明，细胞凋亡是胰岛移植中胰岛细胞损失的主要机制，往往在胰岛分离后早期发生，并在正常培养条件下迅速进展。另一方面，发现在威斯康星大学溶液中冷藏可以抑制细胞凋亡。大鼠胰腺再生研究表明，某些可能包括高血糖的因素被主要胰腺切除术激活，并维持了残余胰腺的再生状态，因为残余胰腺的重量仅暂时增加，并且如果胰管对应于在主要胰腺切除术中切除的胰叶被结扎并留在原处。在干细胞研究中，发现了在小鼠胚胎干细胞的分化研究中获得的神经元样细胞改善帕金森病模型大鼠的症状。还研究了骨髓来源细胞和胰管上皮细胞向胰岛细胞的分化以及骨髓细胞和胰岛细胞的电细胞融合，为今后的研究积累了有趣的知识。